How Is Hunter Syndrome Diagnosed?
Hunter syndrome is a genetic disorder that results due to a defect in X chromosome. This is an X linked recessive disorder. In this disease there is absence of an enzyme named iduronate-2-sulfatase (I2S). This enzyme is necessary for breaking down the glycosaminoglycans (GAGs). When this enzyme is absent, there is accumulation of GAGs in the cells and tissues leading to improper functioning of all the organs and systems of the body. There is alteration in the architecture and functioning of the tissues and cells of the body. Hunter syndrome is also known as mucopolysaccharidosis type II (MPS II).
How Is Hunter Syndrome Diagnosed?
The following signs and symptoms (Red Flag signs and symptoms) are very important for the diagnosis of Hunter syndrome-
Facial dysmorphism- Broad nose, coarse facial features, thickened lips, macroglossia (enlarged tongue), prominence of supraorbital ridges
- Sleep apnea
- Chronic rhinorrhea
- Hearing loss
- Recurrent respiratory tract infections
- Obstruction of upper respiratory tract
- Presence of heart murmurs
- Recurrent otitis media
- Umbilical hernia
- Inguinal hernia
- Stiffness of joints
- Retinal degeneration
- Recurrent watery diarrhea
- Short stature due to developmental delay
- Cognitive impairment
- Behavioral impairment
- Peripheral vascular disease
Skeletal problems- Abnormally thickened bones, carpal tunnel syndrome.
First the Hunter syndrome is diagnosed on the basis of signs and symptoms of the patient. If the signs and symptoms point towards Hunter syndrome, further investigations are done. (1) (2)
Following investigations are performed-
Urinary GAG (glycosaminoglycans) Excretion- In Hunter syndrome there is increased excretion of GAGs in the urine. But if the test turns out to be negative, it does not mean that the disease can be ruled out. Other tests like enzyme activity assays are performed to confirm the diagnosis.
Genetic Testing- In genetic testing the locus of abnormal chromosome is found and it is identified if the female is a carrier or not. This test is very helpful for family planning if the female is found to be a carrier.
Enzyme Activity- When the urinary GAG excretion is found to be high, the next step is enzyme activity. For this test, samples collected are serum or plasma or leukocytes. The activity of iduronate-2-sulfatase (I2S) is detected. The enzyme activity is decreased or very low in Hunter syndrome. Enzyme assay is found to be the gold standard investigation for the diagnosis of Hunter syndrome.
Other Findings Often Seen In Patients With Hunter Syndrome-
Central Nervous System- Seizures may be present. These should be treated with anti-convulsant therapy. Spinal cord compression may be present leading to cervical myelopathy. Decompression must be done to relieve the symptoms.
Cardiovascular System- Bacterial endocarditis is common in patients with Hunter syndrome and so prophylactic treatment must be given. Cardiac valve replacement surgery might be needed in some patients with severe disease.
Ophthalmic Findings- Retinopathy is common due to deposition of GAGs in the retinal epithelial cells. This leads to retinal degeneration and photoreceptor loss. Glaucoma is rare in patients with Hunter syndrome but if present immediate treatment must be started.
Audiologic Findings- Hearing loss is universal in patients with Hunter syndrome. Due to hearing loss, there might be learning difficulty and social detachment. Regular checkup must be done every 6 to 12 months to check the progress of hearing loss and check if there are any ear infections. Proper use of hearing aids must be advised.
Dental Findings- Patient must be advised to take proper dental care. There might be delayed dental eruption.
Respiratory System- If the patient has persistent hypoxia, supplemental oxygen is given. To relieve the symptoms of obstruction, tonsillectomy and also adenoidectomy is usually performed.
Above given signs and symptoms are the most important for the diagnosis of Hunter syndrome. If Hunter syndrome is suspected on the basis of clinical signs and symptoms, then further laboratory investigations are done. The first investigation is urinary excretion of GAGs and after this enzyme assays are done for confirmation.